The objective of this project is to elucidate the relationship between molecular composition and topographic arrangements of membrane building blocks with reference to plasma membrane function. Bioelectrogenesis, transport and many metabolic phenomena are based on the proper associations of membrane proteins and lipids. Membrane ecto-enzymes which are glycoproteins and require a lipophilic environment for optimal activity have been the primary object of these studies. Ecto-phosphoesterhydrolases appear to be a part of a regulatory system which modulates membrane permeability and excitability. Using covalently reacting chemical probes we have been able to achieve selective modifications of membrane ecto-enzymes. Ecto-ATPase and Ecto-5'-nucleotidases appear to be collocated with phosphatidylserine and phosphatidylethanolamine in the membrane. Neoplastic transformation of cells appears to be accompanied by an increase in ecto-ATPase activity and a decrease in ecto-5'-nucleotidase activity. Synaptosome-like vesicles which are enriched in these two ecto-enzymes are exfoliated from cells. These so-called exosomes appear to subserve an intercellular transport function.